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The objective of this study is to evaluate the efficacy and safety of non-suture dural closure using a novel dural substitute (GM111) consisting of polyglycolic acid felt with a fibrin-glue-coated area commensurate in size with the dural defect. This was a non-controlled, open-label, multicenter clinical trial. The efficacy evaluation endpoints were (1) GM111's intra-operative capability to close dural defects and (2) prevention of cerebrospinal fluid (CSF) leakage and subcutaneous CSF retention throughout the postoperative period (evaluated by diagnostic imaging). Patients meeting the following three preoperative and two intra-operative selection criteria were enrolled: (1) between 12 and <75 years of age; (2) the dura is surmised to be defective and in need of reconstruction; (3) informed written consent was obtained from the patient; (4) the surgical wound is class 1; and (5) the size of duraplasty is ≥0.2 cm to <100 cm. Sixty patients were enrolled. The craniotomy site was supratentorial in 77.2%, infratentorial in 12.3% and sellar in 10.5%. The GM111 prosthesis size ranged from 0.24 to 42 cm. To evaluate the efficacy, intra-operative closure was confirmed by Valsalva's maneuver, water infusion, etc., in all patients. CSF leakage and subcutaneous CSF retention throughout the postoperative period were found in four patients. Adverse events for which a causal relationship with GM111 could not be ruled out occurred in 8.8% of the patients. There were no instances of postoperative infection due to GM111. GM111 showed good closure capability and safety when used for non-suture dural closure. Graphical Abstract: [ABSTRACT FROM AUTHOR]

Objective: F-FDG PET has become one of the most important methods for studying malignant lymphoma, but its diagnostic role for primary central nervous system lymphoma (PCNSL) has not been established. The aim of this study was to determine the appropriate cut-off values of FDG uptake and to investigate how corticosteroid administration influences PCNSL. Methods: We retrospectively reviewed 82 patients with contrast-enhanced brain tumors who underwent an FDG PET scan at onset, including 19 PCNSLs. FDG uptake of the lesion was assessed by the maximum standardized uptake value (SUVmax) and the ratio of tumor to normal contralateral cortex activity (T/N ratio). Receiver operating characteristic (ROC) curves were generated from the SUVmax and T/N ratios. To investigate the influence of corticosteroid application before a FDG PET scan, we evaluated the association between the FDG uptake of the lesion and the cumulative dose of corticosteroid administration on 13 PCNSL patients who had received steroid treatment before an FDG PET examination. Results: The mean FDG SUVmax and T/N ratio of PCNSLs were 22.6 and 2.79, respectively, and these values were significantly higher than those of the other malignant brain tumors. ROC analysis indicated that the evaluation of FDG uptake using the T/N ratio was more reliable than the SUVmax with respect to the differential diagnosis. When PCNSL patients went without steroid application before FDG PET, the accuracy of the T/N ratio with a cut-off point of 2.0 was 91.1 %, the sensitivity was 94.7 %, and the specificity was 87.3 %. Although there are no significant differences in the FDG T/N ratio for PCNSL patients with or without steroid treatment, a negative correlation was found between the T/N ratio and cumulative dose of corticosteroid before PET study ( r = −0.71, p = 0.032). Conclusions: We concluded that the T/N ratio was superior to SUVmax for FDG uptake assessment as for distinguishing PCNSLs from other malignant brain tumors; the appropriate T/N ratio cut-off point was 2.0. In addition, FDG uptake could be influenced by cumulative doses of corticosteroid before a PET scan, and thus this fact should be taken into consideration when evaluating FDG PET for PCNSL diagnosis. [ABSTRACT FROM AUTHOR]

Objective: (18)F-FDG PET has become one of the most important methods for studying malignant lymphoma, but its diagnostic role for primary central nervous system lymphoma (PCNSL) has not been established. The aim of this study was to determine the appropriate cut-off values of FDG uptake and to investigate how corticosteroid administration influences PCNSL. Methods: We retrospectively reviewed 82 patients with contrast-enhanced brain tumors who underwent an FDG PET scan at onset, including 19 PCNSLs. FDG uptake of the lesion was assessed by the maximum standardized uptake value (SUVmax) and the ratio of tumor to normal contralateral cortex activity (T/N ratio). Receiver operating characteristic (ROC) curves were generated from the SUVmax and T/N ratios. To investigate the influence of corticosteroid application before a FDG PET scan, we evaluated the association between the FDG uptake of the lesion and the cumulative dose of corticosteroid administration on 13 PCNSL patients who had received steroid treatment before an FDG PET examination. Results: The mean FDG SUVmax and T/N ratio of PCNSLs were 22.6 and 2.79, respectively, and these values were significantly higher than those of the other malignant brain tumors. ROC analysis indicated that the evaluation of FDG uptake using the T/N ratio was more reliable than the SUVmax with respect to the differential diagnosis. When PCNSL patients went without steroid application before FDG PET, the accuracy of the T/N ratio with a cut-off point of 2.0 was 91.1%, the sensitivity was 94.7%, and the specificity was 87.3%. Although there are no significant differences in the FDG T/N ratio for PCNSL patients with or without steroid treatment, a negative correlation was found between the T/N ratio and cumulative dose of corticosteroid before PET study (r = -0.71, p = 0.032). Conclusions: We concluded that the T/N ratio was superior to SUVmax for FDG uptake assessment as for distinguishing PCNSLs from other malignant brain tumors; the appropriate T/N ratio cut-off point was 2.0. In addition, FDG uptake could be influenced by cumulative doses of corticosteroid before a PET scan, and thus this fact should be taken into consideration when evaluating FDG PET for PCNSL diagnosis. [ABSTRACT FROM AUTHOR]

Intracranial germ cell tumours (IGCTs) are a group of rare heterogeneous brain tumours that are clinically and histologically similar to the more common gonadal GCTs. IGCTs show great variation in their geographical and gender distribution, histological composition and treatment outcomes. The incidence of IGCTs is historically five- to eightfold greater in Japan and other East Asian countries than in Western countries, with peak incidence near the time of puberty. About half of the tumours are located in the pineal region. The male-to-female incidence ratio is approximately 3-4:1 overall, but is even higher for tumours located in the pineal region. Owing to the scarcity of tumour specimens available for research, little is currently known about this rare disease. Here we report the analysis of 62 cases by next-generation sequencing, single nucleotide polymorphism array and expression array. We find the KIT/RAS signalling pathway frequently mutated in more than 50% of IGCTs, including novel recurrent somatic mutations in KIT, its downstream mediators KRAS and NRAS, and its negative regulator CBL. Novel somatic alterations in the AKT/mTOR pathway included copy number gains of the AKT1 locus at 14q32.33 in 19% of patients, with corresponding upregulation of AKT1 expression. We identified loss-of-function mutations in BCORL1, a transcriptional co-repressor and tumour suppressor. We report significant enrichment of novel and rare germline variants in JMJD1C, which codes for a histone demethylase and is a coactivator of the androgen receptor, among Japanese IGCT patients. This study establishes a molecular foundation for understanding the biology of IGCTs and suggests potentially promising therapeutic strategies focusing on the inhibition of KIT/RAS activation and the AKT1/mTOR pathway. [ABSTRACT FROM AUTHOR]